Dmrt2, or double-sex and mab-3 related transcription factor 2, is a gene with diverse and significant functions. It belongs to the dmrt gene family, featuring a conserved zinc-finger-like DNA-binding motif (DM domain). Dmrt2 is involved in multiple biological pathways, including endochondral bone formation, somitogenesis, left-right axis determination, adipocyte insulin resistance regulation, gonadal differentiation, and renal intercalated cell differentiation [2,3,4,5]. Its function in these processes is crucial for normal development and physiological balance. Genetic models, especially knockout (KO) mouse models, have been instrumental in uncovering its functions.

In Dmrt2-knockout mice, there are severe rib and vertebral defects, a dwarf phenotype with delayed chondrocyte hypertrophy, and disrupted left-right axis determination due to LRO ciliogenesis and sLRO specification problems [2,3,6]. In the context of insulin resistance, overexpression of Dmrt2 in adipose tissues can attenuate insulin resistance and inflammation in mice, while knockdown in differentiated mouse 3T3-L1 adipocytes enhances insulin resistance [1]. In the kidney, Dmrt2-deficient mice show abnormal type A intercalated cell differentiation, affecting acid-base balance [5].

In conclusion, Dmrt2 plays essential roles in various biological processes, such as skeletal development, axis determination, insulin resistance regulation, and renal function. Studies using KO mouse models have significantly contributed to understanding its role in these processes and related disease conditions, like insulin-resistant metabolic diseases, rib and vertebral malformations, and acid-base imbalance disorders.